Although this project continues, we have not worked on phagocytosis of pneumococci this year because of the complexity of the organism. Pneumococci activate complement in a complex fashion, making it difficult to control the fragment deposited on the organism. Cryptococcus neoformans on the other hand requires opsonization for phagocytosis and is an encapsulated organism that is easily visualized and enumerated. Therefore, in extension of our studies on the C1q interaction with C1q receptors performed in Project 00447-02 we studied the ingestion and killing of the pathogenic fungus Cryptococcus neoformans (CN). The encapsulated blastospores of this organism resist phagocytosis by phagocytes. When coated with specific IgG or C3 fragments though, CN are ingested and killed by human peripheral blood phagocytes. When opsonized with whole human serum, from which all antibody to Cryptococcus had been absorbed, we found deposition of complement n the surface of this organism. The complement coated organism could be phagocytosed proving that in the unactivated cell sufficient complement on the organism surface will allow phagocytosis in the absence of immunoglobulin. Studies were performed in which immunoglobulin receptors on the phagocytes were blocked. This did not block phagocytosis of the complement coated cryptococci. Thus the Cryptococcus is not like a red cell in that immunoglobulin is not required as a second signal to trigger phagocytosis. For the first time, it was found that triggering of the C1q receptor would markedly augment phagocytosis in killing of a microorganism, the Cryptococcus in this case. Phagocytosis and killing were augmented with both IgG and complement coated organisms.